Deimination and expression of peptidylarginine deiminases during cutaneous wound healing in mice
Deimination and expression of peptidylarginine deiminases during cutaneous wound healing in mice
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DOI：
10.1684/ejd.2011.1394
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发表时间：
2011-05-01
影响因子：
2.5
通讯作者：
Simon, Michel
中科院分区：
文献类型：
--
作者：
Coudane, Fanny;Mechin, Marie-Claire;Simon, Michel
脱亚胺是蛋白质结合的精氨酸转化为瓜氨酸的过程，是一种由肽基精氨酸脱亚胺酶(Pad)催化的翻译后修饰。在表皮中表达PAD1、PAD2和PAD3三种Pad，主要脱脂蛋白为微丝蛋白。在各种病理炎症条件下都观察到纤维蛋白的脱亚胺。在这里，我们分析了在皮肤伤口愈合过程中，即在生理性炎症条件下，PADS的表达和蛋白质的瓜氨酸化。对成年小鼠背部皮肤进行全层击打，通过免疫组织化学和Western blotting分析创面愈合情况。PAD1在所有新生表皮中均有表达。PAD3通常在颗粒层表达，但在新生表皮的过度增殖舌中未检测到，但在其分化部分与(Pro)微丝蛋白共定位于大量角质形成细胞层。在再上皮化晚期的新生表皮角质层、凝块和凝块形成的结痂中均可检测到脱脂蛋白。在我们只检测到Pad4的凝块中，显示其中一种去亚胺蛋白是纤维蛋白。凝块蛋白的确定，以及更普遍的伤口愈合和角质形成细胞分化，似乎不依赖于Pad2，如Padi2(-/-)小鼠所显示的那样。
Deimination, the conversion of protein-bound arginines into citrullines, is a post-translational modification catalyzed by a peptidylarginine deiminase (Pad). In the epidermis, three Pads are expressed, namely Pad1, 2 and 3, and the major deiminated protein is filaggrin. Deimination of fibrin has been observed in various pathological inflammatory conditions. Here, we analyzed the expression of Pads and citrullination of proteins during cutaneous wound healing, i.e. in a physiological inflammatory condition. Full-thickness punches were performed on adult mouse back skin, and wound recovery was analyzed over 10 days by immunohistology and western blotting. Pad1 was immunodetected in all the neo-epidermis. Pad3, normally expressed in the stratum granulosum, was not detected in the hyperproliferative tongue of the neo-epidermis, but was shown to be co-localized with (pro)filaggrin in a large number of keratinocyte layers in its differentiating part. Deiminated proteins were detected in the stratum corneum of the neo-epidermis in the late phase of re-epithelialization, and in the clot and the clot-derived scab. In the clot where we only detected Pad4, one of the deiminated proteins was shown to be fibrin. Deimination of the clot proteins, and more generally wound healing and keratinocyte differentiation, seemed to be Pad2-independent, as shown using Padi2(-/-) mice.